Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne's disease (JD), which causes chronic granulomatous enteritis in ruminants. Clinically affected animals develop chronic diarrhea and progressive weight loss that eventually results in death, while subclinically infected animals mainly have decreased production of milk. JD is of tremendous economic importance to the worldwide dairy industry, causing major losses due to reduced production and early culling of animals with estimates of 20% of U.S. dairy herds affected and costs of $220 million per year to the dairy industry (Wells, et al. 2000. J. Am. Vet. Med. Assoc. 216: 1450-1457). Cattle are most susceptible to infection with this organism within the first 6 months of life, but disease typically does not become evident until 3 to 5 years of age. Infection occurs by ingestion of contaminated manure, colostrum, or milk from infected cows (Sweeney, 1996. Vet. Clin. N. Am. Food Anim. Pract. 12:305-312). Fetal infection also occurs, particularly in pregnant cows with advanced disease (Sweeney, et al. 1992. Am. J. Vet. Res. 53:477-480). Moreover, the significance of MAP has increased significantly because of its potential role as a causative agent of Crohn's disease in people (Chamberlin, et al. Aliment Pharmacol Ther 2001; 15(3):337-46; Naser S A, et al. Mol Cell Probes 2002; 16(1):41-8).
The currently approved JD vaccine for field use is an oil suspension of a killed strain of MAP, which has significant limitations. Primarily, the efficacy of this vaccine is questionable with varying results in different vaccination trials Another concern is the interference of whole cell bacterins with diagnostic testing, since vaccinated animals have false positive reactions for tuberculosis and paratuberculosis). Thus, the demand for improved vaccines is on the rise, but they need to be potent and at the same time should not interfere with the diagnosis of tuberculosis and JD. To achieve this goal, several approaches have been tried, which include recombinant vaccines, DNA vaccines and subunit vaccines 13; Shin S J, et al. Infect Immun 2005; 73(8):5074-85). However, there continues to be a need for the development for improved MAP vaccines.